2-aminoarylalkylene-dihydroxy-benzenes



United States Patent O 3,236,893 2-AMINOARYLALKYLENE-DIHYDROXY- BENZENESElkan R. Blout, Belmont, Milton Green, Newton Highlands, Howard G.Rogers, Weston, Myron S. Simon, Newton Center, and Robert B. Woodward,Belmont, Mass., assignors to Polaroid Corporation, Cambridge,

Mass., a corporation of Delaware No Drawing. Filed Mar. 27, 1961, Ser.No. 98,287 7 Claims. (Cl. 260-571) This application is, in part, acontinuation of our copending application Serial No. 612,051, filedSeptember 25, 1956, now US. Patent No. 3,019,107, issued January 30,1962.

This invention relates to novel chemical compounds and more particularlyto certain novel chemical compounds useful as photographic developingagents.

One object of this invention is to provide novel chemical compounds andsuitable syntheses for their preparation.

Another object of this invention is to provide novel photographicdeveloping agents and novel compositions for the development of silverhalide emulsions.

Other objects of this invention will in part be obvious and will in partappear hereinafter.

The invention accordingly comprises the several steps and the relationand order of one or more of such steps with respect to each of theothers, and the products and compositions possessing the features,properties and the relation of elements which are exemplified in thefollowing detailed disclosure, and the scope of the application of whichwill be indicated in the claims.

For a fuller understanding of the nature and objects of the invention,reference should be had to the following detailed description. 7

The novel compounds of this invention may be represented by the formula:

wherein R and R may be the same or different and may be hydrogen oralkyl, preferably lower alkyl such as methyl or ethyl; R is an alkylenegroup, preferably an alkylene group containing no more than' fivecarbons and more preferably an ethylene (CH CH group; Ar is an arylnucleus, such as a benzene vor naphthalene nucleus; each Z is an alkylgroup, preferably lower alkyl such as methyl or ethyl, an alkoxy group,preferably a lower alkoxy group such as methoxy, or halogen, such aschlorine; n is 0, 1 r 2; and Y is an ortho-dihydroxyphenyl or apara-dihydroxyphenyl group which may be substituted by alkyl groups,preferably lower alkyl, or by halogen, e.g., chlorine and bromine.

In the preferred embodiment, the aryl nucleus X is a benzene nucleus,and such compounds may be represented by the formula:

wherein Z, 12, R R R and Y have the same meaning as above.

The following are illustrative examples of compounds falling within thescope of this inventiomand which have been synthesized by one or more ofthe procedures hereinafter described:

(I) p-aminophenethyl-hydroquinone (II) '2- (4 -aminonaphthylethyl)-l1ydr0quinone (III) 2-(p-arninophenethy1)-5-methy1-hydroquinone I OH(IV) 2- (p-amin oplientliyl) -5-chloro-hydroquinone (V) 2- 3-methyl-4-aminophenethyl) -hydroquin'one (VI) 2- (p-aminophenethyl)-5,6-dimethy1hydroquinone (VII) 2- (p-aminophenethyl)-3,5,6-trimethyl-hydroquinone NHr on @CHr-CHIz-Q on (VIII)2-m-aminophenethyhhydroquinone (IX) 2-(maminophenethy1)-5-methyl-hydroqninone (X) 1,2-dihydroxy-4- (p-aminophene'thyl) -benzeneon HzN-QOHz-OH-CH OH (XII) 2-[7-(4'-aminopheny1)-pr0pyl]-hydroquin0ne(I) H (H1 O H (XIII) 2-(4'amino-3-methoxy-phenethy1)-hydr0quinone (XIV)2- ['y- 3-amin0-4-methy1-pheny1) -propy1] hydroquinone,

(XV) 2- (p-aminophenethyl) -6-methy1-hydroquinone (XVI) 2-p-aminophenethy1) --bromo-hydroquinone (XVII)2-(5-amin=onaphthylethy1)-hydroquinone One method of preparing compoundswithin the scope of this invention is by condensing a suitable acidchloride of the formula:

wherein R is an alkylene group, Ar, Z and n have the same meaning asabove, e.g., p-nitrophenylacetyl chloride, with a suitabledihydroxybenzene, which preferably has one hydroxyl group protected,e.g., monobenzyloxyhydroquinone, rearranging the product by a Friesrearrangement to:

on Zn1'&r-R

followed by reduction and removal of any protective group to regeneratethe hydroxyl group. If desired, the alkylene group R may be omitted byusing the acid chloride of the corresponding benzoic acid.

Another method of preparing compounds within the scope of thisinvention, and a preferred method for preparing some of these compounds,is to acylate the appropriate hydroquinone, or a suitable mono ordialkoxy derivative thereof, e.g., p-dimethoxy benzene, with an acid oracid chloride within the above formula using a Friedel-Crafts catalyst,e.g., BF followed by reduction and, where an alkoxy derivative was used,dealkylation to the free hydroquinone.

One may also prepare compounds within the scope of this invention bycondensing a compound of the formula:

Z,..itrGHzCO0H wherein Ar, Z and n have the same meaning as above,

after which the nitro group and the double bond of the prod ct arereduced and the protective groups removed from the hydroxyl groups. Ifdesired, one may use the free dihydroxy laryl aldehyde.

Where the secondary or tertiary alkylated amine derivatives are desired,the amino group may be suitably alkylated in accordance with well-knownalkylating procedures, preferably before removing the protective groups.

The following examples illustrate the preparation of compounds withinthe scope of this invention and are given as illustrations only:

Example 1 A mixture of 100 g. of p-nitrophenyl acetic acid, g. of2,5-dimethoxy benzaldehyde and 20 cc. of piperidine is heated at 160 C.for 6 hours and allowed to cool overnight. The product is taken up incc. of acetic acid and poured into 500 cc. of water, giving a dark redoil. Supernatant liquid is decanted, and the oil is triturated with 100cc. of ethanol. The resultant solid is filtered and crystallized from2,000 cc. of ethanol, giving 52.5 g. of 2,5-dimethoxy-4-nitrostilbene inthe form of red crystals melting at 1l4116 C.

The above product is hydrogenated in 450 cc. of ethyl acetate using 15g. of 5% palladinized barium sulfate. The solvent is then evaporatedoff, giving p-(2',5'dimethoxy-phenethyl)-aniline in the form of an oil.

The thus prepared p-(2,5'-dimethoxy-phenethyl)-aniline is demethylatedby refluxing under nitrogen in 500 cc. of 48% HBr for 4 hours. ExcessHBr is then removed in vacuo, water added and the evaporation repeated.Ethanol is then added and the evaporation repeated again. The residualsolid is dried over potassium hydroxide, giving 54.5 g. ofp-aminophenethyl-hydroquinone hydrobromide in the form of a tan solidmelting at 215 C.

A flask was charged with 500 cc. of 1,2-dichloroethane and 47.1 g. ofanhydrous aluminum chloride. After the resultant mixture had cooled to-5 to 10 C., 53.7 g. of 2,5-dimethoxytoluene diluted with 100 cc. of1,2-dichloroethane was added, dropwise with stirring, while maintainingthis temperature range. Stirring was continued for another 10 minutesafter which 70.5 g. of p-nitrophenylacetyl chloride dissolved in 100 cc.of 1,2-dichloroethane was added, dropwise with stirring, over a30-minute period. The reaction mixture was then poured, with stirring,into a beaker containing 500 g. of ice and stirred for 30 minutes. Theorganic layer which separated was washed with 500 cc. of 5% sodiumcarbonate solution followed by 500 cc. of distilled water. An additional500 cc. of distilled water was added and the resulting mixture was steamdistilled. A brown oil which separated in the steam distillation flasksolidified on cooling to 5 C. to give a brown solid. This solid wasfiltered by suction, partially dried between filter paper, and then wasrecrystallized from 1500 cc. boiling 95% ethanol to give an almostwhite, fluffy crystalline solid. The filtered crystals were washed withcold 95% ethanol, and dried in air at room temperature to give 61.0 g.(55% yield) of p-nitrophenylacetyl- 5-methyl-hydroquinone dimethylether, M.P. 121 C.

10.0 g. of the p-nitrophenylacetyl-S-methyl-hydroquinone dimethyl etherwas dissolved in 200 cc. of glacial acetic acid containing 1.0 g. of 10%palladium on charcoal catalyst and hydrogenated at room temperature atan intial pressure of 45 psi. until the theoretical hydrogen uptake wasobserved. Hydrogenation was then stopped and the acetic acid solutionfiltered directly by suction into 5 cc. of acetic anhydride. The solVQ lWas t.

.5 moved in vacuo on a steam bath. An additional cc. of acetic anhydridewas thoroughly mixed with the straw colored oil and the evaporationprocess repeated. The oil was then dissolved in 100 cc. of absoluteethanol. Removal of the ethanol in vacuo on a steam bath gave a whitesolid (M.P. 133138 C.). This solid was dissolved in 100 cc. of hotmethanol. Water was added to the cloud point and the resultant solutionwas set aside to cool slowly. The white crystals were filtered and driedin air at room temperature to give 9.3 g. (91% yield) of 2-(4-acetamidophenylacetyl)-5-methylhydroquinone dimethyl ether, M.P. 139-142C.

The above product (9.3 g.) was hydrogenated over palladium on charcoalas described earlier in this example. The theoretical amount of hydrogenwas taken up in 2 hours at 80 C. and an initial pressure of 45 psi. Thereaction flask was allowed to cool to room temperature, the catalystfiltered ofl, and the solvent evaporated on a steam bath in vacuo to 100cc. About 100 cc. of distilled water was added to the acetic acidsolution and the resultant milky solution was allowed to crystallizeslowly overnight at room temperature. The white crystals were filtered,washed with water, and dried in air at room temperature to give 7.85 g.(88% yield) of 2-(4'acetamidophenethyl)-5-methylhydroquinone dimethylether, M.P. 120-123 C. This product was hydrolyzed as in Example 1 togive 2-(4'-aminophenethyl)-5-methyl-hydroquinone.

Example 3 180 g. of AlCl was added, over a period of 1 /2 to 2 hours, toa mechanically stirred mixture of 165 g. of p-dimethoxybenzene, 123.5 g.of propionyl chloride, 200 cc. of tetrachloroethane and 50 cc. ofnitrobenzene contained in a flask held in an ice bath. The temperatureof the reaction mixture was kept below 5 C. during the A101 addition.After stirring for 4 hours, the reaction mixture was placed in therefrigerator overnight. The reaction mixture was then poured onto amixture of ice and hydrochloric acid and stirred thoroughly. Theresulting aqueous and organic layers were separated, and the aqueouslayer was extracted with ether. The ether extract was combined with theorganic layer, washed twice with 3 N sodium hydroxide and once withwater. After drying over magnesium sulfate, the ether was driven off andthe residue distilled on a water aspirator. The resulting product,2,S-dimethoxy-propiophenone, is a pale yellow liquid (B.P. 160162 C. .at12 mm. Hg) which darkens on standing.

A flask was charged with 97 g. of 2,5-dimethoxy propiophenone and 75.5g. of p-nitrobenzaldehyde dissolved in 1500 cc. of 2B ethanol (dry). Theflask was chilled in an ice bath and 20 g. of NaOH in 100 cc. of waterwere added slowly with stirring. After a few minutes, the desired4-nitro-2',5'-dimethoxy-fi-methyl-chalcone:

CHM)

crystallized out. The filtered crude product was washed with cold 80%ethanol and recrystallized from ethanol to give yellow needles, M.P.144150 C.

A Parr shaker bottle was charged with g. of 4-nitro-2',5'-dimethoxy-B-methyl-chalcone, 1 g. of 10% palladium on charcoalcatalyst, 100 cc. of acetic acid and 40 cc. of acetic anhydride.Hydrogen was passed in and the mixture was shaken until the theoreticalquantity of hydrogen for the nitro group and the double bond wasabsorbed. The reaction mixture was filtered through a Celite pad andevaporated. Methanol was added to the oily residue and this solution wasevaporated. The resulting oil was taken up in 100 cc. of acetic acid andreturned to the shaker bottle with 1 g. of 10% Pd/C catalyst. Hydrogenwas CHaO as a white powder, M.P. 99101 C. 5 g. of this product, 50 cc.of acetic acid and 100 cc. concentrated hydrochloric acid were refluxed,under nitrogen, for about 20 hours. The reaction was evaporated, 213ethanol added to the residue and the solution evaporated again. Theresulting oil was taken up in ethanol and precipitated with ether. Theether was removed and the flask containing the oil was warmed and placedunder aspirator vacuum. The oily material solidified, and the solid wasscraped from the flask and dried in a vacuum desiccator to give 3.4 g.yield) of 2-[a-(4'-aminophenyl)-fl-methylpropyl]- hydroquinonehydrochloride as a light tan material melting, with decomposition, at150 C.

Example 4 In a modification of the procedure described in Example 3, 9.7g. of 2,5-dimethoxy-propiophenone, 8.15 g. of p-acet-amidobenzaldehydeand cc. of methanol were placed in a flask and heated on a steam bath toeffect solution. 2.7 g. of sodium methoxide in about 20cc. of methanolwas added, and the flask was plugged with glass wool and allowed tostand at room temperature for 3 days. At this point, crystals started toform. The separated yellow solid (M.P. 148153 C.) was recrystallizedfrom methanol/water. Heating of the reaction mixture on a steam bath for15 to 20 minutes after it had been standing for 24 hours was found tohasten precipitation of the product chalcone. This chalcone washydrogenated overnight in glacial acetic acid using a Pd/ c catalystfollowing the procedure described in Example 3.

Example 5 2-[ot-(4-aminophenyl)-propyl]-hydroquinone was prepared in amanner similar to that described in Example 3, except that theintermediate chalcone, i.e., 2,5-dimethoxy- 4'-nitrochalcone, wasprepared as follows: 25 g. each of p-nitroacetophenone and2,S-dimethoxy-benzaldehyde in 500 cc. of 2B ethanol (dry) was stirred ina flask until solution was effected. The flask was cooled below 10 C.and a mixture of 50 cc. of 3 N NaOH and 50 cc. of 2B ethanol was addedslowly. Stirring was continued at this temperature for 3 hours after theaddition was completed. The reaction mixture was brought to roomtemperature slowly and then filtered. The solids were washed with waterand recrystallized from ethanol. Hydrogenation of this chalcone waseffected in acetic acid over Pd/ C cata lyst; the theoretical hydrogenuptake was absorbed after about 2 hours. The catalyst was filtered ofl,acetic anhydride added and the flask stoppered and allowed to standovernight at room temperature. Upon addition of water, a cloud appeared;upon scratching, a white solid precipitated out and was filtered off andwashed with water. Hydrolysis of the product (recrystallized from thesame solvent mixture, M.P. 116l18 C.) gave the desired product.

Example 6 2 (4'-amino-3-methoxy-phenethyl)-hydroquinone was prepared asfollows: m-cresol was nitrated according to the procedure in Annalen,vol. 259, p. 208 (1890), giving a mixture of isomers, from which2-nitro-5-methyl-phenol was separated. This compound then was treatedwith dimethyl sulfate in the usual manner to give 3-metlhoxy-4-nitro-toluene, which was converted into 3-methoxy-4- nitro-phenylaceticacid as follows: to a 500 cc. flask containing 50 cc. of 2B ethanol wasadded 81 g. of sodium methoxide. 19.0 cc. of ethyl oxalate was added tothe stirred solution, followed by 18.1 g. of 3-methoxy-4-nitrotoluene.The solution was refluxed for 15 minutes, cooled, 100 cc. of wateradded, the alcohol removed in vacuo and the solution filtered. To thefiltrate (kept at 30 C. or lower) was added 6 cc. of 30% hydrogenperoxide, and the solution was stirred until there was no furtherevolution of gas. The solution was then filtered, and the filtrate wasacidified and extracted with ether. After drying, the ether was removed.The product could be crystallized from either water or ether-hexane.Analysis of the product (M.P. 1l9l21 C.) as C H NO showed:

Calculated 51. 2 4. 3 6. 6 Found 51.1 4. 3 6.

Gentisalde'hyde dibenzyl ether was prepared as follows: a mixture of 121g. of benzenesulfonylgentisyl hydrazide dibenzyl ether and 1360 cc. ofethylene glycol was heated with stirring in a 5 liter flask to 160 C. atwhich temperature solution was complete. The heating mantle was removedand 160 g. of anhydrous sodium carbonate was added at once. There wasvigorous frothing, lasting several minutes. When this frothing hadsubsided, 750 cc. of water was cautiously added to the hot mixture, andthe flask was cooled. The cooled solution was poured into 3750 cc. ofice and water, to which was then added 190 cc. of 3 N sodium hydroxide.The solids were filtered off and desiccated over P 0 The dried product(91 g.) was crystallized from hexane by extraction with three 2.5-literportions of boiling solvent, followed by filtration (hot), concentrationof the clear filtrate to about 500 cc., chilling, and filtration of theprecipitate that separated. 50 g. of yellow powder, M.P. 8791 C., wasobtained (64% yield).

In a 300 cc. three-necked flask were placed 6.36 g. of gentisaldehydedibenzyl ether, 4.22 g. of 3-methoxy-4- nitro-phenylacetic acid, and 2cc. of piperidine. The mixture was heated in a Woods metal bath to abath temperature of 160 C., maintained at that temperature for an hourand forty-five minutes, and then cooled. The product was extracted withether, the ether solution washed with dilute hydrochloric acid, water, 3N sodium hydroxide and water. The product then was dried, filtered, andthe solvent removed. The 2,5-dibenzyloxy3'- methoxy-4-nitrostilbenesolid product, after crystallization from acetic acid-water, melted at8790 C. and gave a nitrogen analysis of 2.9% (calculated 3.0%). 3.7 g.of this stilbene product in 50cc. of ethyl acetate was reduced in a Parrshaker over 1 g. of 5% palladium-on-barium sulfate catalyst until thetheoretical hydrogen uptake (for reduction of the nitro group, thedouble bond, and cleavage of the benzyl ethers) was observed. Thedesired 2 (4 amino 3'-methoxy-phenethyl)hydroquinone was then recoveredin a manner similar to that described in the previous examples.

As previously noted, the novel compounds of this invention are useful asphotographic developing agents, and this use is disclosed and claimed inour previously mentioned copending application, Serial No. 612,051.

The novel compounds of this invention are also useful as anti-oxidantsin petroleum products. The compounds wherein R and R both are hydrogenare useful as intermediates, for example, in the preparation of thecorresponding O-acylated compounds disclosed and claimed in thecopending application of Milton Green and Helen P.

Husek, Serial No. 805,673, filed April 13, 1959, as acontinuation-in-part of Serial No. 612,063, filed September 25, 1956(now abandoned), which copending application issued as U.S. Patent No.3,019,254 on January 30, 1962. These O-acylated compounds, in turn, areuseful as intermediates in the preparation of azo dyes, as disclosed andclaimed in the copending application of Elkan R. Blout, Milton Green andHoward G. Rogers, Serial No. 612,045, filed September 25, 1956, nowabandoned and replaced by Serial No. 145,978, filed October 18, 1961,now U.S. Patent No. 3,134,764.

It will be noted that the dialkyl ether intermediates, e.g.,p-(2,5-dimethoxyphenethyl)-aniline, as well as the N-acylated dialkylether intermediates, e.g., 2-[a-(4' acetamidophenyl) p methyl-propyl]hydroquinone dimethyl ether, also are novel compounds.

3-methyl-2,5-dimethoxybenzaldehyde, an intermediate useful in thesynthesis of compounds within the scope of this invention, may beprepared according to the procedures described in the copendingapplication of Milton Green, Adnan A. Sayigh and Henri Ulrich, SerialNo. 25,559, filed April 29, 1960.

Since certain changes may be made in the above processes, products andcompositions without departing from the scope of the invention hereininvolved, it is intended that all matter contained in the abovedescription shall be interpreted as illustrative and not in a limitingsense.

What is claimed is:

1. Compounds selected from the group consisting of compounds within theformula:

wherein R is an alkylene group containing no more than 5 carbons, each Zis selected from the group consisting of lower alkyl, lower alkoxy andchlorine groups, n is selected from the group consisting of 0 and 1, Aris an aryl nucleus selected from the group consisting of benzene andnaphthalene nuclei, and Y is selected from the group consisting ofunsubstituted, lower alkyl-substituted, chlorine substituted and brominesubstituted 0 dihydroxyphenyl and p-dihydroxyphenyl groups andunsubstituted, lower-alkyl substituted, chlorine-substituted andbrominesubstituted o-di-lower alkoxyphenyl and p-di-lower alkoxyphenylgroups.

2. Compounds as defined in claim 1, wherein Ar is a benzene nucleus.

3. p-Aminophenethyl-hydroquinone.

4. 2- ['y- (4-a.minophenyl -propyl] -hydroquinone.

5. 2-(p-aminophenethyl)-5-methyl-hydroquinone.

6. 2- (3 '-unethyl-4'-aminopheuethyl) -hydroquinone.

7. 2-(4-aminonaphthylethyl)-hydroquinone.

References Cited by the Examiner UNITED STATES PATENTS 2,497,248 2/1950Vogt et al 260575 2,631,167 3/1953 Werner 260575 2,796,435 6/1957Goldberg et al 260570.7 2,878,291 3/1959 Cavallini et al. 2605752,983,605 5/1961 Corley 9629 3,019,1'07 1/1962 Blout et a1. 96663,076,808 2/1963 Blout et a1 9629 OTHER REFERENCES Beilstein, OrganischeChemie, vol. 13, page 811, Dec. 8, 1930.

Drefahl et al., Ann, vol. 598, pages 174-85 (1956).

Fulnegg et al., Amer. Photo, vol. 21, pages 324-6 (1927).

James et al., P.S.A. Journal, vol. 15, page 136 (1949).

Mees, The Theory of the Photographic Process, pages 5466 and 578 (1954).

CHARLES B. PARKER, Primary Examiner.

JOSEPH P. BRUST, Examiner.

1. COMPOUNDS SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS WITHIN THEFORMULA: